Postsynaptic movement disorders: clinical phenotypes, genotypes, and disease mechanisms

• Published in: Journal of inherited metabolic disease Vol. 41; no. 6; pp. 1077 - 1091
• Main Authors: Abela, Lucia, Kurian, Manju A.
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.12.2018; Blackwell Publishing Ltd
• Subjects: Animals; Biochemistry; Biomarkers; Brain diseases; Childrens health; Chorea - genetics; Chorea - metabolism; Convulsions & seizures; Corpus Striatum - metabolism; Dopamine - metabolism; Dopamine receptors; Dystonic Disorders - genetics; Dystonic Disorders - metabolism; Epilepsy; Gene expression; Genotype; Genotypes; Human Genetics; Humans; Intellectual disabilities; Internal Medicine; Medicine; Medicine & Public Health; Metabolic Diseases; Metabolism; Mice; Movement disorders; Movement Disorders - genetics; Movement Disorders - metabolism; Mutation; Neostriatum; Neurological disorders; Neurons; Neurosciences; Neurotransmitters; Pediatrics; Phenotype; Phenotypes; Proteins; Review; Signal Transduction; Spiny neurons; Synaptic Transmission
• ISSN: 0141-8955; 1573-2665; 1573-2665
• DOI: 10.1007/s10545-018-0205-0

Movement disorders comprise a group of heterogeneous diseases with often complex clinical phenotypes. Overlapping symptoms and a lack of diagnostic biomarkers may hamper making a definitive diagnosis. Next-generation sequencing techniques have substantially contributed to unraveling genetic etiologies underlying movement disorders and thereby improved diagnoses. Defects in dopaminergic signaling in postsynaptic striatal medium spiny neurons are emerging as a pathogenic mechanism in a number of newly identified hyperkinetic movement disorders. Several of the causative genes encode components of the cAMP pathway, a critical postsynaptic signaling pathway in medium spiny neurons. Here, we review the clinical presentation, genetic findings, and disease mechanisms that characterize these genetic postsynaptic movement disorders.